Determinação de polimorfos de fexofenadina pelas técnicas Raman, NIR e DRX

Abstract

Organic polymorphs are common and present different physicochemical properties to each other. In pharmaceutical research, the polymorphism has a particular focus by allowing a molecule in a particular solid pharmaceutical formulation presents different solubility and stability. Traditionally, the most used technique in the characterization of polymorphs is the X-ray diffraction. However, in the interests of pharmaceutical quality assurance, low cost, non-destructive and handheld techniques, based on vibrational spectroscopy, have been used to develop methodologies for polymorphic characterization, both in raw materials and finished product. The main objective of this work was to develop methodologies to quantify the two polymorphic forms of fexofenadine hydrochloride in raw material and in pharmaceutical formulation, in the form of powder and tablet. To this end, firstly, we performed crystallization, characterization and study of polymorphic fexofenadine hydrochloride. Then, Raman spectroscopy and powder X-ray diffraction were used with multivariate regression PLS (Partial Least Squares), for the simultaneous determination of two polymorphs of fexofenadine hydrochloride in mixture of raw material (first application) and in a powder pharmaceutical formulation containing microcrystalline cellulose, starch, magnesium stearate, TiO2 and povidone (second application). Both for raw material and powder pharmaceutical formulation, the X-ray diffraction shown to be more accurate than Raman spectroscopy, presenting lower values of RMSECV and RMSEP and most appropriated fitting (R2). In a third application the NIR-CI (Near Infrared Chemical Imaging) spectroscopy coupled with PLS and MCR-ALS (Multivariate Curve Resolution - Alternating Least Squares) allowed the construction of distribution maps of concentration and determination of polymorphs of fexofenadine hydrochloride in tablets.